Progesterone, but not 17-alpha-hydroxyprogesterone caproate, inhibits human myometrial contractions.
OBJECTIVE
The aim was to determine whether progesterone (P4) or 17-alpha-hydroxyprogesterone caproate (17P) directly inhibit human uterine contractility in vitro and thereby clarify their mechanisms of action.


METHODS
Myometrial tissues were suspended in organ chambers and exposed for 2 to 20 hours to varying concentrations of P4 or 17P or solvent. Contractile activity was registered, stored, and analyzed. Dose response curves were then generated for P4 or 17P at various times.


RESULTS
P4 significantly inhibited spontaneous contractility dose dependently. The inhibition was not blocked by RU486 but was reversible after washing. Surprisingly, 17P dose dependently stimulated contractility. HPLC and GC-MS methods were used to determine the detectable concentrations of progestins in the baths.


CONCLUSIONS
P4, at concentrations equivalent to those present in the placenta and uterus, inhibit spontaneous myometrial contractility in vitro by nongenomic mechanisms.
Ruddock
Nicole K
NK
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX, USA.
Shi
Shao-Qing
SQ
Jain
Sangeeta
S
Moore
Gradie
G
Hankins
Gary D V
GD
Romero
Roberto
R
Garfield
Robert E
RE
D019326:17-alpha-Hydroxyprogesterone / Q000494:pharmacology*; D000328:Adult; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D008600:Menstruation-Inducing Agents / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D009215:Myometrium / Q000187:drug effects* / Q000502:physiology; D011374:Progesterone / Q000494:pharmacology*; D011372:Progestins / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects*
D008600:Menstruation-Inducing Agents; D011372:Progestins; D015735:Mifepristone; D011374:Progesterone; D019326:17-alpha-Hydroxyprogesterone